In applicant's co-pending parent application, Ser. No. 782,724, now U.S. Pat. No. 4,710,490 the disclosure of which is incorporated by reference herein, compositions which exhibited efficacy in causing angiogenesis were described. Among the tests which showed such efficacy were CAM assays, involving live chick embryos. This application alluded to co-pending application Ser. No. 642,624, filed Aug. 20, 1984, now U.S. Pat. No. 4,199,788, the disclosure of which is also incorporated by reference herein. This application discloses an animal model (the "cat leg" model) which was used to demonstrate in vivo efficacy of a chloroform/methanol fraction of an omental tissue extract. The "cat leg" model which is described therein, is the animal model described in th Detailed Description of Preferred Embodiments which follows, infra.
The omentum was reported to be effective in supplying blood to ischemic areas of the body as early as 1903. See, e.g. DeRenzi, et al., Berl. Klin. Woch. 40:773-775 (1903); Morrison, Brit. Med. J. 1:76-78 (1906); Wilkie, Brit. Med. J. 2:1103-1106 (1911). Later work, e.g., O'Shaughnessy, Brit. J. Surg. 23:665-670 (1936); Knock, Surg. Form. 9:230-232 (1958), shows that predicted omentum might provide collateral circulation to the heart. Later work by Vineberg and associates, Can. Med. Assoc. J. 87:1074-1076 (1962); Can. Med. Assoc. J. 90:717-722 (1964); Am. Heart J. 72:79-93 (1966); Dis. Chest. 54:315-322 (1968); Surgery, Gynecol. Obstetrics 137:564-578 (1973), reported treatment of patients with coronary/artery disease in which direct mycocardial implantation of the internal mammary artery with peri-coronary omental strips.
Current interest has centered around using the omentum for revascularization of the central nervous system. For example, Goldsmith, et al., Surgery 88:732-736 (1980); Stroke 9:224-229 (1978); Am. J. Surg. 130:317-320 (1975); Am. J. Surg. 129:263-265 (1975); Arch. Surg. 106:695-698 (1973); Rev. Surg. 24:379-380 (1967) have shown that vascularization occurs at an omental cerebral and omental spinal cord interface which allows for the addition of an extensive new cource of blood to the brain and spinal cord, in spite of the absence of ischemia in these organs. Following this, Goldsmith, et al., JAMA 252:2034-2036 discovered an omental lipid fraction which possesses patent angiogenic activity.
Folch, et al., J. Biol. Chem 226:497-509 (1957) teach a method for isolating and purifying lipids in animal tissue. References to "Folch fractions" and "Folch apparatus" made herein refer to the methods set forth in this paper. Ledden, et al., Meth. Enzym. 83:119-139 (1982) teach the isolation and analysis of gangliosides in general, while Williams, et al., J. Neurochem. 35:226-269 (1980) show the use of C18 cartridges during ganglioside isolation. Kannagi, et al., J. biol. Chem. 257:14,865-14,874 (1982) show that glycosphingolipids of human erythrocytes react with monoclonal antibodies to developmental antigen SSEA-1
None of the prior art has taught or suggested, however, that localized vascular perfusion could be obtained using omental lipid materials, or other lipid material. Localized vascular perfusion to traumatized tissue is desirable. While the site of such perfusion decrease is sometimes easily detectable, frequently it is not. Additionally, sometimes, while the site of reduced perfusion is detectable, application of a circulation or perfusion enhancing drug locally is difficult. Material which increases perfusion systemically is clearly not desirable in many cases, as will be immediately apparent to one skilled in the art.
Hence, it is an object of this invention to provide compositions useful in increasing localized perfusion to traumatized tissue in mammals.
It is a further object of this invention to provide a method of increasing perfusion, using said composition.
It is a further object of the invention to present a method for delivery of said compositions to particular sites of traumatized tissue for increased localized perfusion, using systemic applications.
How these and other objects of the invention are accomplished will be readily ascertained by review of the materials which now follow.